IP Library › Granted Patent US 12,264,194
Granted Patent B2
US 12,264,194 · App. 17/438,828 · Granted Apr 1, 2025

Decreasing

Inventors: Mark Esser (Gaithersburg, MD); Alexey Ruzin (Gaithersburg, MD); Hasan Jafri (Gaithersburg, MD); Kathryn Shoemaker (Gaithersburg, MD); Bret Sellman (Gaithersburg, MD); Li Yu (Gaithersburg, MD)
Assignee: MedImmune, LLC
C07K16/1271C12Q1/686C12Q1/689A61K2039/505A61K2039/545C07K2317/52C12Q2600/106
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,264,194
App. No.
17/438,828
Granted
Apr 1, 2025
Kind
B2
Abstract

The present disclosure is directed to methods of treating subjects colonized with S aureus with an anti-alpha toxin antibody or antigen-binding fragment thereof. The methods can decrease the incidence of infection attendant to the presence of S. aureus in the subject.

Claims (20)

1. A method of treating a subject colonized with Staphylococcus aureus ( S. aureus ), the method comprising administering an antibody or antigen-binding fragment thereof that binds to S. aureus alpha toxin (AT) to the subject, wherein polymerase chain reaction (PCR) has been used to detect the level of S. aureus in a sample that was obtained from the subject prior to the administering, wherein the sample has a level of S. aureus that does not exceed a level of S. aureus that correlates to a polymerase chain reaction (PCR) cycle threshold (Ct) value of 29 or above, wherein the PCR Ct value of 29 corresponds to a sample concentration of S. aureus that does not exceed 1700 colony forming units (CFU)/mL of S. aureus , and wherein the antibody or antigen-binding fragment thereof that binds to S. aureus AT comprises a variable heavy chain (VH) complementarity determining region (CDR) 1 comprising the amino acid sequence of SEQ ID NO: 1, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:2, a VH CDR3 comprising the amino acid sequence of SEQ ID NO:3, a variable light chain (VL) CDR1 comprising the amino acid sequence of SEQ ID NO:4, a VL CDR2 comprising the amino acid sequence of SEQ ID NO:5, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:6.

2. The method of claim 1 , wherein the antibody or antigen-binding fragment thereof that binds to S. aureus AT comprises a VH comprising the amino acid sequence of SEQ ID NO:7 and a VL comprising the amino acid sequence of SEQ ID NO:8.

3. The method of claim 1 , wherein the subject has S. aureus pneumonia.

4. The method of claim 1 , wherein the PCR detects S. aureus protein A.

5. The method of claim 1 , wherein the subject is taking antibiotics.

6. The method of claim 1 , wherein the sample was obtained from the lower respiratory tract of the subject.

7. The method of claim 1 , wherein the sample contains bacteria that would not grow in a culture to identify S. aureus.

8. The method of claim 1 , wherein the S. aureus is antibiotic resistant.

9. The method of claim 1 , further comprising determining whether the S. aureus is methicillin-resistant.

10. The method of claim 1 , wherein the antibody or antigen binding fragment thereof that binds to S. aureus AT comprises a Fc region with a M252Y, S254T, and T256E (YTE) mutation.

11. The method of claim 1 , wherein the antibody or antigen-binding fragment that binds to S. aureus AT is a monoclonal antibody or antigen-binding fragment.

12. The method of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a heavy chain amino acid sequence of SEQ ID NO:11 and a light chain amino acid sequence of SEQ ID NO: 10.

13. The method of claim 3 , wherein the antibody or antigen-binding fragment thereof comprises a heavy chain amino acid sequence of SEQ ID NO:11 and a light chain amino acid sequence of SEQ ID NO:10.

14. The method of claim 2 , wherein the antibody or antigen binding fragment thereof that binds to S. aureus AT comprises a Fc region with a M252Y, S254T, and T256E (YTE) mutation.

15. The method of claim 2 , wherein the antibody or antigen-binding fragment that binds to S. aureus AT is a monoclonal antibody or antigen-binding fragment.

16. The method of claim 2 , wherein the PCR detects S. aureus protein A.

17. The method of claim 2 , wherein the subject is taking antibiotics.

18. The method of claim 2 , wherein the sample was obtained from the lower respiratory tract of the subject.

19. The method of claim 2 , wherein the sample contains bacteria that would not grow in a culture to identify S. aureus.

20. The method of claim 2 , wherein the S. aureus is antibiotic resistant.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 7, 2024
From: ESSER, MARK; RUZIN, ALEXEY; JAFRI, HASAN; SHOEMAKER, KATHRYN; SELLMAN, BRET; YU, LI
To: MEDIMMUNE LLC
Reel/Frame 069181/0958 →
Continuity (2)
Provisional Application 62817934 · Mar 13, 2019
Related Publication 20220127338A1 · Apr 28, 2022
References Cited (50)
US 9527905B2 · Sellman et al. · 2016 [cited by applicant]
US 9845348B2 · Sellman et al. · 2017 [cited by applicant]
US 9879070B2 · Sellman et al. · 2018 [cited by applicant]
US 10457724B2 · Sellman et al. · 2019 [cited by applicant]
US 10730934B2 · Sellman et al. · 2020 [cited by applicant]
US 10759849B2 · Sellman et al. · 2020 [cited by applicant]
US 11059884B2 · Tkaczyk et al. · 2021 [cited by applicant]
US 11168132B2 · Sellman et al. · 2021 [cited by applicant]
US 11168133B2 · Tkaczyk et al. · 2021 [cited by applicant]
US 11447543B2 · Sellman et al. · 2022 [cited by applicant]
US 11578119B2 · Tkaczyk et al. · 2023 [cited by applicant]
US 20110165172A1 · Yarranton et al. · 2011 [cited by applicant]
US 20190077851A1 · Jafri et al. · 2019 [cited by applicant]
US 20220089699A1 · Tkaczyk et al. · 2022 [cited by applicant]
CN 103443285A · 2013 [cited by applicant]
WO WO2012109285A2 · 2012 [cited by applicant]
WO WO2013093693A1 · 2013 [cited by applicant]
WO WO2014074540A2 · 2014 [cited by applicant]
WO WO2015196011A1 · 2015 [cited by applicant]
WO WO2017075188A2 · 2017 [cited by applicant]
WO WO2020076789A2 · 2020 [cited by applicant]
WO WO2020185986A1 · 2020 [cited by applicant]
Coppens, J., et al., “Comparison of GeneXpert MRSA/SA ETA assay with semi-quantitative and quantitative cultures and nuc gene-based qPCR for detection of [cited by applicant]
Co-Pending U.S. Appl. No. 17/152,725, inventors Jafri, H., et al., filed Jan. 19, 2021 (Not Published). [cited by applicant]
Esperatti, M., et al., “Nosocomial Pneumonia in the Intensive Care Unit Acquired by Mechanically Ventilated versus Nonventilated Patients,” Am. J. Resp. Crit. Care Med. 182(12):1533-1539, American Thoracic Society, Unit… [cited by applicant]
Foletti, D., et al., “Mechanism of action and in vivo efficacy of a human-derived antibody against [cited by applicant]
Francois, B., et al., “Safety and tolerability of a single administration of AR-301, a human monoclonal antibody, in ICU patients with severe pneumonia caused by [cited by applicant]
Hazenbos, W.L., et al., “Novel staphylococcal glycosyltransferases SdgA and SdgB mediate immunogenicity and protection of virulence-associated cell wall proteins,” PLOS Pathog. 9(10):e1003653, PLOS, United States (2013). [cited by applicant]
Hua, L., et al., “Assessment of an anti-alpha-toxin monoclonal antibody for prevention and treatment of [cited by applicant]
Hua, L., et al., “MEDI4893* Promotes Survival and Extends the Antibiotic Treatment Window in a [cited by applicant]
Karauzum, H., et al., “Synthetic human monoclonal antibodies toward staphylococcal enterotoxin B (Seb) protective against toxic shock syndrome,” J. Biol. Chem. 287(30):25203-25215, Elsevier, Netherlands (2012). [cited by applicant]
Lowy, F.D., “ [cited by applicant]
Mashburn, L.M., et al., “ [cited by applicant]
Rouha, H., et al., “Five birds, one stone: neutralization of a-hemolysin and 4 bi-component leukocidins of [cited by applicant]
Ruzin, A., et al., “2160: Performance of the Cepheid Rapid PCR Test for Patient Screening and Association with Efficacy of Suvratoxumab, A Novel Anti- [cited by applicant]
Spellberg, B., and Talbot, G., “Recommended Design Features of Future Clinical Trials of Antibacterial Agents for Hospital-Acquired Bacterial Pneumonia and Ventilator-Associated Bacterial Pneumonia,” Clinical Infectious… [cited by applicant]
Wilke, G.A., and Wardenburg, J.B., “Role of a disintegrin and metalloprotease 10 in [cited by applicant]
Adhikari, R.P., et al., “Novel structurally designed vaccine for [cited by applicant]
Becker, R.E.N., et al., “Tissue-Specific Patterning of Host Innate Immune Responses by [cited by applicant]
Bhakdi, S.J., and Tranum-Jensen, J., “Alpha-toxin of [cited by applicant]
Wardenburg, J.B., and Schneewind, O., “Vaccine protection against [cited by applicant]
Inoshima, N., et al., “Genetic requirement for ADAM10 in severe [cited by applicant]
Oganesyan, V., et al., “Mechanisms of Neutralization of a Human Anti-α-toxin Antibody,” J. Biol. Chem., 289(43):29874-29880, American Society for Biochemistry and Molecular Biology, United States (Oct. 2014). [cited by applicant]
Powers, M.E., et al., “Synergistic Action of [cited by applicant]
Powers, M.E., et al., “ADAM10 mediates vascular injury induced by [cited by applicant]
Ragle, B.E., et al., “Anti-Alpha-Hemolysin Monoclonal Antibodies Mediate Protection against [cited by applicant]
Tkaczyk, C., et al., “Identification of Anti-Alpha Toxin Monoclonal Antibodies That Reduce the Severity of [cited by applicant]
Yu, X-Q., et al., “Safety, Tolerability, and Pharmacokinetics of MEDI4893, an Investigational, Extended-Half-Life, Anti- [cited by applicant]
International Search Report and Written Opinion mailed Jun. 15, 2020, in International Application No. PCT/US2020/022226, European Patent Office, Netherlands, 14 pages. [cited by applicant]
English language translation of Office Action for Chinese Patent Application No. 202080034698.2, dated Sep. 7, 2024, 3 pages. [cited by applicant]